Synthesis and crystal structure of bis(2-phthalimidoethyl)ammonium chloride dihydrate

The title compound is a phthalimide-protected polyamine with a protonated central nitrogen atom. The crystal packing features a hydrogen-bond network, a two-coordinated chloride ion, and off-set π–π stacking.


Chemical context
The title compound was synthesized by Frederick Mann in 1934(Mann, 1934. It has been a key component for the synthesis of tripodal amines (Lundin et al., 2004;Blackman, 2005), Schiff base macrocycles (Keypour et al., 2008), MRI contrast agents of gadolinium(III) (Cheng et al., 2000), and as a tricyclic host for anions (Kang et al., 2010). Recently, it has also been used to functionalize graphene oxide (Ramesh & Jebasingh, 2019), build a nano-polymer dendrimer to uptake salicylic acid (Arshadi et al., 2019), and construct a fluorescent ligand (Saga et al., 2020). The compound itself has formed a complex with manganese as a superoxide dismutase mimetic (Piacham et al., 2014). A variety of phthalimide compounds have been of interest because of the variety of supramolecular interactions that can exist (Howell et al., 2003).

Structural commentary
The molecular structure of the title compound is shown in Fig. 1. The compound is a protonated polyamine with two phthalimide groups protecting the terminal nitrogens. It crystallizes in the monoclinic space group P2 1 /c. The planes of the two phthalimide units (N1/C1-C8 and N3/C13-C20) make a dihedral angle of 22.07 (3) . These units point in opposite directions to each other from the perspective of the central nitrogen atom. The central tetrahedral nitrogen atom (NH 2 ) forms hydrogen bonds with a water molecule and the chloride ion.

Database survey
A search of the Cambridge Structural Database (version 5.41, update of July 2022; Groom et al., 2016) for related compounds with a phthalimide unit gave 2881 hits. A search for the skeletal structure of N(CH 2 CH 2 NH 2 ) 2 resulted in 1707 hits, while the structure with protonated amines + HN(CH 2 CH 2 NH 3 + ) 2 resulted in 182 hits. One of these structures is the triprotonated diethylenetriamine trichloride (ETACLA01; Ilioudis et al., 2000). This structure includes one chloride ion that is two-coordinate and two chlorides that are three-coordinate. A search for an amine with two phthalimide groups had 24 hits. The structure of a diphthalimidodiethylammonium and hydrogen phthalate complex showed stabilization by offsetstacking, carbonyl-carbonyl, and hydrogen-bonding interactions (REVZAT; Barrett et al., 1995). Hydrogen bonding occurs within the complex unit and connects adjacent units. The offsetstacking between phthalimide units is characterized by CÁ Á ÁC distances ranging from 3.297-3.592 Å . We have previously reported a phthalimide-protected polyamine that exhibits offsetstacking (Holmberg et al., 2021).

Synthesis and crystallization
Following a previous protocol (Utz et al., 2008), 5.0 mL (48 mmol) of diethylenetriamine were dissolved in 50 mL of methanol. To this, 15.0 g (101 mmol) of phthalic anhydride were slowly added, which turned the solution clear and yellow. The solution was kept at 333 K with minimal fluctuations and stirred for approximately 45 min. The solution became cloudy. It was removed from heat and stirred at room temperature for 7 days. A Bü chner funnel and filter paper were saturated with MeOH, and the round-bottom flask was rinsed with MeOH prior to vacuum filtration. The precipitate was a pale-yellow solid. It was rinsed four times with 25 mL of MeOH and 4 Â 25 mL of acetone to give 9.609 g of the product (55% yield).

Figure 1
The molecular structure of the title compound, showing 50% probability ellipsoids.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq